title: Treatment of patients with advanced cancer with the natural killer cell line NK-92.
abstract: OBJECTIVE
  Natural killer (NK) cells, either naive or genetically engineered, are increasingly considered for cellular therapy of patients with malignancies. When using NK cells from peripheral blood, the number of expanded NK cells can be highly variable and the need for NK cell enrichment can make the process expensive. The NK-92 cell line (CD56+/CD3-) that was isolated from a patient with lymphoma has predictable high cytotoxic activity and can be expanded under good manufacturing practice conditions in recombinant interleukin-2.
  
  
  METHODS
  Fifteen patients (age, 9-71 years) with advanced, treatment-resistant malignancies, either solid tumors/sarcomas (n = 13) or leukemia/lymphoma (n = 2), received two infusions of NK-92 cells, given 48 h apart. Three cohorts of patients were treated with escalating doses of NK-92 cells (n = 7 at 1 × 10(9), n = 6 at 3 × 10(9) and n = 2 at 1 × 10(10) cells/m(2)).
  
  
  RESULTS
  No infusion-related or long-term side effects were observed. The dose of 10(10) cells/m(2) was considered the maximum expandable cell dose with the use of an established culture bag system. Three fourths of patients with lung cancer had some anti-tumor response. Only one patient of seven had development of human leukocyte antigen antibodies. The persistence of NK-92 cells (male origin) in the circulation was confirmed by Y chromosome-specific polymerase chain reaction in two female patients.
  
  
  CONCLUSIONS
  Infusions of NK-92 cells up to 10(10) cells/m(2) were well tolerated. Despite the allogeneic nature of NK-92, development of human leukocyte antigen antibodies in these patients with cancer appears to be rare. The cells can persist in the recipient's circulation for at least 48 h. Some encouraging responses were seen in patients with advanced lung cancer.
authors.affiliation: Institute for Transfusion Medicine and Immunohematology, Goethe University Hospital, Frankfurt am Main, Germany; German Red Cross Blood Donation Service, Baden-Württemberg-Hessen, Germany. Electronic address: ttonn@blutspende.de.
authors.forename: Torsten
authors.initials: T
authors.lastname: Tonn
authors.forename: Dirk
authors.initials: D
authors.lastname: Schwabe
authors.forename: Hans G
authors.initials: HG
authors.lastname: Klingemann
authors.forename: Sven
authors.initials: S
authors.lastname: Becker
authors.forename: Ruth
authors.initials: R
authors.lastname: Esser
authors.forename: Ulrike
authors.initials: U
authors.lastname: Koehl
authors.forename: Meinolf
authors.initials: M
authors.lastname: Suttorp
authors.forename: Erhard
authors.initials: E
authors.lastname: Seifried
authors.forename: Oliver G
authors.initials: OG
authors.lastname: Ottmann
authors.forename: Gesine
authors.initials: G
authors.lastname: Bug
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064987:Cell- and Tissue-Based Therapy; D002648:Child; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007694:Killer Cells, Natural / Q000166:cytology / Q000637:transplantation*; D007945:Leukemia, Lymphoid / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012509:Sarcoma / Q000473:pathology / Q000628:therapy*; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000379:methods
keywords: NK-92; cancer; cellular immunotherapy; natural killer cell; phase I clinical trial